Electrophysiological effects of dronedarone (SR33589), a noniodinated benzofuran derivative, in the rabbit heart - Comparison with amiodarone
Electrophysiological effects of dronedarone (SR33589), a noniodinated benzofuran derivative, in the rabbit heart - Comparison with amiodarone
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DOI：
10.1161/01.cir.100.22.2276
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发表时间：
1999-11-30
期刊：
影响因子：
37.8
通讯作者：
Singh, BN
中科院分区：
文献类型：
--
作者：
Sun, W;Sarma, JSM;Singh, BN
背景：为了克服胺碘酮（AM）的副作用，合成了胺碘酮的非碘化类似物dronedarone （SR）。本研究比较了其与AM在兔心脏中的电生理作用。方法与结果：5组动物（每组n=7）连续3周，每天口服其中1种方案：(1)对照组，仅为车辆；(2) AM50 mg/kg (AM50)；(3) AM100 mg/kg (AM100)；(4) SR50 mg/kg (SR50)；(5) SR100 mg/kg （SR100）。分别于用药前和用药前3周记录心电图。用微电极技术记录离体乳头肌和窦房结的动作电位。在组织浴中研究不同浓度SR （0 ~ 10 μ mol/L）对对照组（n=5）的短期影响。采用重复测量的方差分析比较不同周期长度下50% （APD(50)）和90% （APD(90)）复极动作电位持续时间和上冲程dV/dt （V-max）。与对照组相比，AM和SR增加了RR、QT和QTc间期(P
Background-To overcome the side effects of amiodarone (AM), its noniodinated analogue, dronedarone (SR), was synthesized. In this study, its electrophysiological effects were compared with those of AM in rabbit hearts.Methods and Results-Five animal groups (n=7 each) for 3 weeks received daily oral treatment of 1 of these regimens: (1) control, vehicle only; (2) AM 50 mg/kg (AM50); (3) AM 100 mg/kg (AM100); (4) SR 50 mg/kg (SR50); and (5) SR 100 mg/kg (SR100). ECGs were recorded before drug and at 3 weeks of drug before euthanasia. Action potentials were recorded from isolated papillary muscle and sinoatrial node by microelectrode techniques. The short-term effects were studied in controls (n=5) at various concentrations of SR (0 to 10 mu mol/L) in tissue bath. Action potential duration at 50% (APD(50)) and 90% (APD(90)) repolarization and upstroke dV/dt (V-max) at various cycle lengths were compared by ANOVA with repeated measures. Compared with control, AM and SR increased RR, QT, and QTc intervals (P